Peptides are a group of biomolecules that have been broadly used as reagents in many biomedical research areas, therapeutic drugs in the treatment of diseases, and diagnostic agents in detecting pathogens and biomarkers. Two methods are generally used to synthesize peptides. One is chemical synthesis and the other is the recombinant expression. Chemical synthesis has been used for the preparation of a variety of therapeutic peptides including corticorelin, parathyroid hormone (PTH), glucagon-like peptide-1 (GLP-1) and its analogs exenatide and liragultide, enfuvirtide, calcitonin, bivalirudin, ziconotide, sermorelin, somatorelin, secretin, teduglutide, and insulin. This method needs multiple condensation reactions of amino acid fragments to generate peptides and requires tedious protection, deprotection, and purification processes. So far, most of commercial peptides with few than 50 amino acid residues are manufactured in this way. Given the increasing demand for peptides in pharmaceutical industry and biomedical research, the prices of amino acid fragments used for chemical synthesis of peptides have been continuously ascending. Therefore, for daily used therapeutic peptide drugs such as GLP-1 analogs, it will be difficult to maintain their affordable prices in the future. Although chemical synthesis of a peptide with more than 50 amino acid residues is technically achievable, the low yields and the exceeding amount of organic waste generated during the synthesis make it economically unfavourable. So far, most of peptides with more than 50 amino acid residues are recombinantly expressed in cell hosts such as bacterial, yeast, insect, and mammalian cells. For many years, it has been a common practice to use fusion proteins for the expression of peptides. The readily available carrier proteins include glutathione-S-transferase (WO94/04688 and Ray et al., BioTechnology, 11, 64, 1993), ribulokinase (U.S. Pat. No. 5,206,154 and Callaway et al., Antimicrob. Agents & Chemo., 37, 1614-1919, 1993), gp-55 protein (Gram H. et al., Biotechnology, 12, 1017-1023, 1994), ketosteroid isomerase (Kuliopulos A. et al., J. Am. Chem. Soc., 116, 4599-4607, 1994), ubiquitin (Pilon A. et al., Biotecnol. Prog. 13, 374-379, 1997), bovine prochymosin (Hauht et al., Biotechnolo. Bioengineer., 7, 55-61, 1998), GB1 domain (Darrinm et al., Biochemistry, 41, 7267-7274, 2003), RNA-binding protein (Sharon M. et al., Protein Exp. And Purif., 24, 374-383, 2002), SH2 domain (Fairlie W. et al., Protein Exp. And Purif. 26, 171-178, 2002), cellulose binding domain, small ubiquitin-like modifier, intein, bactericidal/permeability-increase protein, carbonic anhydrase (U.S. Pat. No. 5,962,270 and WO97/29127), alpha-lactalbumin (WO95/27782), beta-glactosidase (Shen S., PNAS, 281, 4627-4631, 1984), and chloramphenicol acetyltransferase (Dykes C. et al., European Journal of Biochemistry, 174, 411-416, 1988). These fusion carriers have been selected for their relatively high expression levels and fast folding processes in host cells. Although useful, the final yields of peptides recombinantly expressed using fusion carrier proteins typically do not exceed 100 mg/L. In addition, current available fusion protein methods for peptide expression also have many technical problems especially for the production of peptides smaller than 50 amino acid residues (Vileghe et al., Drug Discovery Today, 15, 40-56, 2010).
It would be highly desirable to provide with a new carrier protein overcoming the limitations of other existing carrier proteins for the production of recombinant peptides.